Evaluation of the role of proline residues flanking the RGD motif of dendroaspin, an inhibitior of platelet aggregation and cell adhesion

The Biochemical Journal
X LuV V Kakkar

Abstract

The effect of a panel of proline mutants of dendroaspin, an inhibitor of platelet aggregation and cell adhesion, including A(42)-dendroaspin, A(47)-dendroaspin, A(49)-dendroaspin, A(42,47)-dendroaspin and A(47,49)-dendroaspin, was investigated using platelet-aggregation and cell-adhesion assays. Here we show that a single alanine-for-proline substitution did not affect potency when measured as the ability either to inhibit platelet aggregation induced by ADP (IC(50) approximately 170 nM) or to block transfected A375-SM cell adhesion to fibrinogen in the presence of Mn(2+) as compared with wild-type dendroaspin. By comparison, double proline substitution with alanines significantly reduced the potency in both assays by approx. 5-8-fold. These observations, therefore, suggest that proline residues flanking the RGD motif in dendroaspin and other RGD-containing venom proteins, e.g. disintegrins, may contribute to maintaining a favourable conformation for the solvent-exposed RGD site for its recognition by integrin receptors.

Citations

Jul 31, 2010·Toxicon : Official Journal of the International Society on Toxinology·R Manjunatha Kini, Robin Doley
Apr 19, 2015·Biochemical Pharmacology·Yuanjun ZhuYinye Wang
Aug 17, 2005·Insect Biochemistry and Molecular Biology·Ivo M B FrancischettiJosé M C Ribeiro
Aug 8, 2002·Clinical and Experimental Pharmacology & Physiology·R Manjunatha Kini
Apr 29, 2014·Chemical Biology & Drug Design·Ashok K Kulkarni, Rajendra P Ojha

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